Spatial epidemiology and serologic cohorts increase the early detection of leprosy.

BACKGROUND: Leprosy remains an important public health problem in some specific high-burden pockets areas, including the Brazilian Amazon region, where it is hyperendemic among children. METHODS: We selected two elementary public schools located in areas most at risk (cluster of leprosy or hyperendemic census tract) to clinically evaluate their students. We also followed anti-PGL-I seropositive and seronegative individuals and households for 2 years to compare the incidence of leprosy in both groups. RESULTS: Leprosy was detected in 11 (8.2 %) of 134 school children in high risk areas. The difference in the prevalence was statistically significant (p < .05) compared to our previous findings in randomly selected schools (63/1592; 3.9 %). The 2-year follow-up results showed that 22.3 and 9.4 % of seropositive and seronegative individuals, respectively, developed leprosy (p = .027). The odds of developing overt disease in seropositive people were 2.7 times that of negative people (p < .01), indicating that a follow-up of 10 seropositives has a >90 % probability to detect at least one new case in 2 years. The odds of clinical leprosy were also higher in "positive houses" compared to "negative houses" (p < .05), indicating that a follow-up of ten people living in households with at least one seropositive dweller have a 85 % probability to detect at least one new case in 2 years. CONCLUSIONS: Targeted screening involving school-based surveillance planned using results obtained by spatial analysis and targeted household and individual continuous surveillance based on serologic data should be applied to increase the early detection of new leprosy cases.

Antimicrobial Activity on Streptococcus mutans and Enterococcus faecalis of Cyperus articulatus Ethanolic Extracts.

Oral diseases are one of the biggest public health problems worldwide, caused by opportunistic pathogens such as Streptococcus mutans and Enterococcus faecalis. Cyperus articulatus (priprioca) is a plant conventionally used in traditional medicine in the Amazon region. However, little is known about the possible dentistry-related uses of extracts from the rhizomes and solid waste generated by the extraction of essential oils from this vegetable. This study aimed to investigate the chemical composition of volatile compounds and antimicrobial activity through the Minimum Inhibitory Concentration test (MIC and assessment of the toxicity by Hens Egg Test-Chorion Allantoic Membrane (HET-CAM) of the ethanolic extracts from Cyperus articulatus intact rhizomes and solid waste. We identified sesquiterpenes as the main constituents, strong antimicrobial activity of the ethanolic extract of intact rhizomes against S. mutans (MIC = 0.29 mg/mL), moderate antimicrobial activity against E. faecalis of the extract obtained from the solid waste (MIC = 1.17 mg/mL), and absence of toxicity for both tested extracts. The absence of irritation and the antibacterial activity of the ethanolic extract from C. articulatus rhizomes and solid waste reveal its potential for use in the alternative control of bacteria that cause oral infections and may present economic viability as a raw material for dental products.

Antiplasmodial Activity of Hydroalcoholic Extract from Jucá (Libidibia ferrea) Pods.

Malaria is an infectious and parasitic disease caused by protozoa of the genus Plasmodium, which affects millions of people in tropical and subtropical areas. Recently, there have been multiple reports of drug resistance in Plasmodium populations, leading to the search for potential new active compounds against the parasite. Thus, we aimed to evaluate the in vitro antiplasmodial activity and cytotoxicity of the hydroalcoholic extract of Jucá (Libidibia ferrea) in serial concentrations. Jucá was used in the form of a freeze-dried hydroalcoholic extract. For the cytotoxicity assay, the(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method with the WI-26VA4 human cell line was used. For the antiplasmodial activity, Plasmodium falciparum synchronized cultures were treated with serial concentrations (0.2 to 50 µg/mL) of the Jucá extract. In terms of the chemical composition of the Jucá extract, gas chromatography coupled to mass spectrometry measurements revealed the main compounds as ellagic acid, valoneic acid dilactone, gallotannin, and gallic acid. The Jucá hydroalcoholic extract did not show cytotoxic activity per MTT, with an IC50 value greater than 100 µg/mL. Regarding the antiplasmodial activity, the Jucá extract presented an IC50 of 11.10 µg/mL with a selective index of nine. Because of its antiplasmodial activity at the tested concentrations and low toxicity, the Jucá extract is presented as a candidate for herbal medicine in the treatment of malaria. To the best of our knowledge, this is the first report of antiplasmodial activity in Jucá.

Anti-Inflammatory Potential of the Oleoresin from the Amazonian Tree Copaifera reticulata with an Unusual Chemical Composition in Rats.

Copaifera reticulata Ducke is a popularly known species known as copaíba that is widely spread throughout the Amazon region. The tree yields an oleoresin which is extensively used in local traditional medicine mainly as an anti-inflammatory and antinociceptive agent. The aim of the present study was to assess the anti-inflammatory potential of this oleoresin obtained from a national forest in the central Amazon which presented an unusual chemical composition. The chemical composition of volatile compounds of oleoresin was analyzed by gas chromatography-mass spectrometry. The acute toxicity assay was performed with a single dose of 2000 mg/kg. The anti-inflammatory potential was evaluated by carrageenan-induced paw edema and air pouch assays using four different C. reticulata oleoresin concentrations (10, 100, and 400 mg/kg). The exudate was evaluated for nitrite concentration through the colorimetric method and for TNF-α, IL-1ß, and PGE2 by ELISA. C. reticulata oleoresin collected in the Amazonian summer contained six major sesquiterpene compounds (ß-bisabolene, cis-eudesma-6,11-diene, trans-α-bergamotene, ß-selinene, α-selinene, and ß-elemene) and was nontoxic at a dose of 2000 mg/kg, showing low acute toxicity. Different from oleoresin obtained from other sites of the Brazilian Amazon, the major volatile compound found was ß-Bisabolene with 25.15%. This ß-Bisabolene-rich oleoresin reduced the formation of paw edema induced by carrageenan and reduced the global number of cells in the air pouch assay, as well as exudate volume and nitrite, TNF-α, IL-1ß, and prostaglandin E2 levels (p < 0.05). C. reticulata oleoresin with a high ß-Bisabolene concentration showed anti-inflammatory activity, reducing vascular permeability and consequently edema formation, and thus reducing cell migration and the production of inflammatory cytokine, confirming its traditional use by local Amazonian communities.

Latent leprosy infection identified by dual RLEP and anti-PGL-I positivity: Implications for new control strategies.

The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas.

In vitro and in vivo antimalarial activity of the volatile oil of Cyperus articulatus (Cyperaceae)

Malaria is a disease of global tropical distribution, being endemic in more than 90 countries and responsible for about 212 million cases worldwide in 2016. To date, the strategies used to eradicate this disease have been ineffective, without specific preventive measures such as vaccines. Currently, the existing therapeutic arsenal is limited and has become ineffective against the expansion of artemisinin-resistant Plasmodium, demonstrating the need for studies that would allow the development of new compounds against this disease. In this context, we studied the volatile oil obtained from rhizomes of Cyperus articulatus (VOCA), a plant species commonly found in the Amazon region and popularly used as a therapeutic alternative for the treatment of malaria, in order to confirm its potential as an antimalarial agent by in vitro and in vivo assays. We cultured Plasmodium falciparum W2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains in erythrocytes and exposed them to VOCA at different concentrations in 96-well microplates. In vivo antimalarial activity was tested in BALB/c mice inoculated with approximately 106 erythrocytes infected with Plasmodium berghei. VOCA showed a high antimalarial potential against the two P. falciparum strains, with IC50 = 1.21 µg mL-1 for W2 and 2.30 µg mL-1 for 3D7. VOCA also significantly reduced the parasitemia and anemia induced by P. berghei in mice. Our results confirmed the antimalarial potential of the volatile oil of Cyperus articulatus. (AU)